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首页> 外文期刊>Nature >T-cell-expressed Proprotein Convertase Furin Is Essential For Maintenance Of Peripheral Immune Tolerance
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T-cell-expressed Proprotein Convertase Furin Is Essential For Maintenance Of Peripheral Immune Tolerance

机译：T细胞表达的前蛋白转化酶弗林蛋白酶对于维持外周免疫耐受至关重要

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摘要

Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins. It is induced in activated T cells and is reported to process a variety of substrates including the anti-inflammatory cytokine transforming growth factor (TGF)-β1 (refs 2-4), but the non-redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T-cell development but impaired the function of regulatory and effector T cells, which produced less TGF-β1. Furin-deficient T regulatory (T_(reg)) cells were less protective in a T-cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin-deficient effector cells were inherently over-active and were resistant to suppressive activity of wild-type T_(reg) cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non-redundant, essential function in regulating TGF-β1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.
机译：弗林蛋白酶是促进原蛋白水解成熟的七个原蛋白转化酶家族成员之一。它在活化的T细胞中被诱导，据报道可加工多种底物，包括抗炎细胞因子转化生长因子（TGF）-β1（参考2-4），但弗林蛋白酶相对于其他前蛋白转化酶具有非冗余功能T细胞不清楚。在这里，我们显示条件性删除T细胞中的弗林蛋白酶允许正常的T细胞发育，但损害了调节性T细胞和效应T细胞的功能，从而减少了TGF-β1的产生。弗林蛋白酶缺陷型T调节（T_（reg））细胞在T细胞转移性结肠炎模型中的保护作用较弱，并且无法在正常T细胞中诱导Foxp3。此外，弗林蛋白酶缺陷效应细胞固有地过度活跃，并且对野生型T_reg细胞的抑制活性有抵抗力。因此，我们的结果表明，弗林蛋白酶在维持外周耐受性中是必不可少的，这至少部分是由于其非冗余的调节TGF-β1产生的基本功能。靶向弗林蛋白酶已经成为恶性和传染病的一种策略。我们的结果表明，抑制弗林蛋白酶可能会激活免疫反应，但可能导致外周耐受性下降。

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  • 来源
    《Nature》 |2008年第7210期|p.246-250|共5页
  • 作者

    Marko Pesu; Wendy T. Watford; Lai Wei; Lili Xu; Ivan Fuss; et al;

  • 作者单位

    Molecular Immunology and Inflammation Branch, National Institute for Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 关键词

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